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The Lancet Oncology

Tuesday, May 19, 2009

New diagnostic procedures: a new, quick test for prostate cancer

Prostate cancer is the most common cancer diagnosed in men in the UK and many other developed countries, including the United States. In the UK 35,000 men are diagnosed each year with prostate cancer. To emphasis the gravity of the disease, one man dies every hour of prostate cancer in the UK. African Caribbean men are three times more likely to develop prostate cancer than Caucasian men. In the United States, the estimated number of new cases prostate cancer is more than 192,000 with 27,000 deaths.

A new, fast, diagnostic procedure
Researchers have developed the test by using light energy to measure the level of citrate in fluid samples from the prostate gland. The technique could provide the basis of a rapid means of detecting prostate cancer in the future. Almost a quarter of male cancers in the UK are diagnosed as prostate cancer and more than 10,000 men die from the disease each year.

Scientists, led by Prof David Parker from Durham University’s Chemistry Department, have worked with experts from the University of Maryland, USA to develop the technique that measures the wavelength of light as it is shone through diluted samples of body fluids.

The research team, funded by the North East Proof of Concept Fund and the EPSRC, believe that the technique which can measure, with speed and accuracy, how citrate levels fall in the prostate gland as cancer develops, could also find use for the diagnosis of other medical conditions, associated with poor kidney function.

Prof Parker said: “Citrate provides a significant biomarker for disease that may provide a reliable method for screening and detecting prostate cancer, and for the monitoring of people with the disease. This technique could form the basis of a simple screening procedure for prostate cancer that could be used in outpatient departments at local hospitals.”

His team have shone light into over 100 different chemical structures to see how they function and respond to the presence of certain important bioactive species. They have looked particularly closely at how citrate and lactate bind to luminescent structures within fluids. Citrate and lactate are vital for our bodies’ metabolism for normal function. Citrate provides energy for cells and the amount found in the prostate varies considerably due to an enzyme called m-aconitase which transforms it. This enzyme is very sensitive to zinc and, in prostate cancer sufferers, zinc levels are depressed and the enzyme switches on again.

Prof Leslie Costello from the University of Maryland said: “Citrate is formed in cell metabolism processes which alter as cancers grow. The analysis of the citrate concentration of prostatic fluid can provide an accurate way to screen and diagnose prostate cancer. Since citrate concentrations decrease markedly early in malignancy, this technique makes it possible to analyse what’s happening quickly in the early and treatable stage of prostate cancer. It shows much promise as a clinical tool.”

The new test requires only a microlitre of fluid and the sample can be easily measured in an optical instrument. Using samples from male volunteers, the researchers have developed a portable instrument that can give results in 3 minutes.

The team’s challenge has been how to accurately measure changes in the amount of citrate or lactate in fluid samples using the technique. The early results are promising and the team intends to look at the analysis of other body fluids. A possible way forward is to examine the citrate levels in seminal fluid samples, which are made up of 50% prostate fluid.

Technology Transfer
The University has launched a spin-out company called FScan Ltd to develop the technique and to seek commercial backing. The team has looked at 20 samples so far and verified the analysis in every case. The next stage is to work with a local hospital and examine samples from 200 volunteers to see whether the first Durham results correlate.

Prof Parker says: “It’s been a complex process to develop the technique but we’re very optimistic about it. Ultimately, this could provide an accurate method of screening for prostate cancer in men that could be carried out in 3-minutes once a biopsy has been obtained from the patient at a hospital outpatient department.”

The Prostate Cancer Charity believes that this new, three minute test could effectively help to diagnose prostate cancer.

The discovery follows the invention in 2006 by Durham University Professor Douglas Newton of a Urine Flow Meter. The UFlow Meter helps men to assess if they have a restricted rate of urine flow - one of the warning signs of prostate problems.

The establishment of FScan Ltd is part of the University’s aim to enhance the exploitation of the Intellectual Property generated by high quality research activities.

Tim Hammond, Head of Technology Transfer at Durham University, said: '”We quickly realised the potential of this research and have worked closely with Professor Parker and his team to secure initial proof of concept funding through NorthStar Equity Investors and the North East Proof of Concept Fund and to establish FScan Limited as the vehicle to validate and commercialise the technology.”

John Neate, Chief Executive of The Prostate Cancer Charity, an organization striving for a world where lives are no longer limited by prostate cancer,explains: “This is early stage research, with the citrate levels of only 20 samples being tested. The results of a biopsy take around two weeks to come back to a patient and the main benefit of this new potential test would be one of speed. If the findings of further research in a large group of men remain consistent with these early results, the test could add something beneficial to the diagnostic tools currently available. Men could have a clearer idea of whether they have the disease, before the biopsy results confirm this. The full biopsy results would still be necessary, however, to confirm whether a man has an aggressive or non-aggressive form of the disease."

“The benefit of the test to men living with non-aggressive forms of prostate cancer, who are being treated with active surveillance, is less clear. This new test, which involves the insertion of a needle into the prostate under local anaesthetic, is an invasive procedure when compared to the current practice of monitoring the progression of the disease using the PSA blood test. The researchers hope to able to refine the test by using samples of seminal fluid which may be easier to obtain. If this was the case, it would be easier to see how this test could take a useful place in clinical practice."

“The acceptability of the test as a broader screening tool is problematic, given its invasive nature.”

Process for testing
1. Sample of prostatic fluid taken from patient in hospital using local anaesthetic
2. 200 fold dilution of 1 microlitre of sample with a buffer solution into pre-coated disposable cuvettes.
3. Optical spectroscopy on the sample, using a versatile bench top instrument with easy to use software.
4. Reading of results after 3 min measurement cycle directly reading out actual citrate concentration.

The sample is taken from the prostate gland – this is part of the biopsy procedure during clinical analysis in urology.

For more information, read the following PubMed abstracts:

Other resources:

Information for your patients:

Fig. 1 : Range of citrate levels measured using the new optical probe

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